The studies are proposed with a view to contribute to the understanding of thyroid gland physiology in health and the nature, basis and significance of its alterations in the diseases of various organ systems. Tissues of man and the rat contain a thyroid hormone binding inhibitor (THBI), an inhibitor of extrathyroidal conversion of thyroxine (T4) to more active 3,5,3'-triiodothyronine (T3) (IEC), and an inhibitors of phagocytosis (PI) of Escherichia coli by normal human leucocytes. We shall characterize these inhibitory activites, determine if they are the same or distinct, estimate quantitatively their release into the circulation of patients with nonthyroid illness (NTI), study of NTI patients the correlation of serum levels of inhibitors with alterations in thyroid hormones levels, with severity of NTI and mortality and determine the mechanisms and sequence of events involved in the release of inhibitors from tissues into the circulation. An experimental model of NTI will be developed in the rat to more closely study the temporal changes and the relationship of the three inhibitors with thyroid hormone changes in NTI and with prognosis. Other studies related to the enzymic activity that metabolizes T4 to 3,3',5'-T3 (reverse T3, rT3). Skin and cerebral cortex are the richest tissues in this enzymic activity. We shall characterize the activity in skin, study its regulation, alterations with age, hair cycle and skin disorders. Similar studies will also be carried out in erebral cortex. We shall develop methods to study serum and urinary concentration, metabolic clearance rate (MCR) and production rate of thyronine (TO), the ultimate product of thyroid hormone metabolism. We hypothesize that measurement of T0 in serum and/or urine may be a simple, rapid and convenient method for assessment of overall thyroid hormone secretion. We shall also investigate that usefulness of iodinated radio-contrast agents, e.g. sodium ipodate, a potent inhibitor of extrathyroidal conversion of T4 to more active T3, in the management of hyperthyroidism.